Uses
ATC0175 is a MCHR1, SR-1A and SR-2B inhibitor.
Biological Activity
Potent, selective and orally active melanin-concentrating hormone receptor 1 (MCH 1 ) antagonist (IC 50 values are 13.5 and > 10000 nM for MCH1 and MCH2 receptors respectively). Exhibits anxiolytic and antidepressant activity in rodents. Also displays affinity for 5-HT 2B and 5-HT 1A receptors (IC 50 values are 9.66 and 16.9 nM respectively).
in vitro
assays showed that this compound is a potent antagonist with a high affinity for mch1r. the receptor binding and the functional assay (mch-induced increase in [ca2+]) indicated that atc0175 is a noncompetitive antagonist at mch1rs 1.
in vivo
atc0175 displayed anxiolytic effects in numerous animal models of anxiety including the social interaction test, elevated plus-maze test, maternal separation-induced vocalization and stress-induced hyperthermia. in addition, atc0175 treatment also exhibited antidepressant effects in the forced swimming test 2.
References
1. semple g, tran ta, kramer b, et al. pyrimidine-based antagonists of h-mch-r1 derived from atc0175: in vitro profiling and in vivo evaluation. bioorganic & medicinal chemistry letters. 2009;19(21):6166-6171.2. chaki s, yamaguchi j, yamada h, et al. atc0175: an orally active melanin-concentrating hormone receptor 1 antagonist for the potential treatment of depression and anxiety. cns drug reviews. 2005;11(4):341-352.
